Role of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis in brain-mediated compensatory antiinflammatory response
Christian Woiciechowsky, Stefan Ruprecht, Wolf-Dietrich Döcke, and Hans-Dieter Volk (Germany)
Local infection or trauma induce a local inflammatory response. The release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF- a ), interleukin-1beta (IL-1 ß ), and IL-6 activates an inflammatory cascade improving wound healing and antimicrobial defence. Overwhelming response, however, can result in systemic inflammatory response syndrome (SIRS) and septic shock. In order to control the potentially harmful inflammatory response, the immune system can release several antiinflammatory mediators like IL-10, IL-1 receptor antagonist (ra), and soluble TNF- a receptors. TNF- a , IL-1 ß and prostaglandins by themselves are powerful inducers of the compensatory antiinflammatory response syndrome (CARS). However, there are evidences that in addition to the autoregulatory pathways of the immune cells the delicate balance between pro- and antiinflammatory response is controlled by central mechanisms. Hence, a bidirectional communication between the immune and central nervous system (CNS) exists and is most evident in the increase in secretion of different neuromodulators and neurohormones that follows systemic inflammation. Moreover, in vitro studies demonstrate that these neuromediators, especially glucocorticoids and catecholamines, predominantly decrease the secretion of proinflammatory cytokines (IL-1, IL-6 and TNF- a ) and increase the release of antiinflammatory mediators like IL-10 and transforming growth factor-beta. Consequently, the activation of the neuroimmune pathways reduces the intensity of the immune response and prevents an overwhelming inflammatory immune reaction. If the immunoinhibitory CNS pathways are activated without systemic inflammation, however, a brain-mediated immunodepression can develop. This activation can result from the production of cytokines in the brain following infection, injury, and ischemia or in response to different stressors (life events, depression, anxiety etc) or directly from brain stem irritation. In summary, mediators of the CNS are implicated in the regulation of immune functions and play a role in both conditioning the host’s response to endogenous or exogenous stimuli and generating a brain-mediated immunodepression.
Biomed Rev 2000; 11: 29-38.
Received 27 September 2000 and accepted 15 November 2000.
Correspondence and reprint requests to Dr Christian Woiciechowsky, Department of Neurosurgery, Charité -Campus Virchow-Klinikum, Humboldt University of Berlin, Augustenburger Platz 1, D-13353 Berlin,Germany. Tel.: 49 30 45060714,
Fax: 49 30 45060977,